• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.913-921
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• 2005

In this study, we investigated gene expression patterns induced by Ailanthus altissima extract and compared it with Gleevec, a well-known anti-leukemia drug, in K562 chromic leukemia cells. Ailanthus altissima extract(100 ug/ml) and Gleevec(50 ug/ml) were treated to cells for 1h, 2h, 4h, and 16h and total RNA was extracted. Gene expressions were evaluated using cDMA microarray, in which 24,000 genes were spotted. Hierarchical clustering analysis showed that expression of genes included in two clusters were increased or decreased time dependently by both Ailanthus altissima extract and Gleevec. Genes included in another cluster were induced by Ailanthus altissima extract but not by Gleevec. In biological process analysis, expression of genes involved in apoptosis, growth arrest and DNA-damage were increased, but genes stimulating cell cycle were decreased. This study provides comprehensive comparison of the patterns of gene expression changes induced by Ailanthus altissima extract and Gleevec in K-562 leukemia cells.

• Molecular & Cellular Toxicology
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• v.1 no.4
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• pp.248-255
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• 2005

To understand the response of cancer cells to anticancer drugs at the gene expression level, we examined the gene expression changes in response to five anticancer drugs, 5-fluorouracil, cytarabine, cisplatin, paclitaxel, and cytochalasin D in NCI-H460 human lung cancer cells. Of the five drugs, 5-fluorouracil had the most distinctive gene expression signature. By clustering genes whose expression changed significantly, we identified three clusters with unique gene expression patterns. The first cluster reflected the up-regulation of gene expression by cisplatin, and included genes involved in cell death and DNA repair. The second cluster pointed to a general reduction of gene expression by most of the anticancer drugs tested. A number of genes in this cluster are involved in signal transduction that is important for communication between cells and reception of extracellular signals. The last cluster represented reduced gene expression in response to 5-fluorouracil, the genes involved being implicated in DNA metabolism, the cell cycle, and RNA processing. Since the gene expression signature of 5-fluorouracil was unique, we investigated it in more detail. Significance analysis of microarray data (SAM) identified 808 genes whose expression was significantly altered by 5-fluorouracil. Among the up-regulated genes, those affecting apoptosis were the most noteworthy. The down-regulated genes were mainly associated with transcription-and translation-related processes which are known targets of 5-fluorouracil. These results suggest that the gene expression signature of an anticancer drug is closely related to its physiological action and the response of caner cells.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.1
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• pp.7-12
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• 2006

Telomerase activation is detected in most cancerous cells; hence, telomerase is a highly selective target for cancer therapy, which plays an important role in the apoptotic process. We have previously reported that the ginseng saponin metabolite, Compound K (20-O-D-glucopyranosyl-20(S)-protopanaxadiol, IH901), inhibits cell proliferation by inducing apoptosis and cell cycle arrest at the $G_1$ phase. The present study investigated the regulation of telomerase activity in Compound K treated U937 cells. Compound K treatment caused a reduction in telomerase activity and down-regulated the human telomerase reverse transcriptase (hTERT) gene, resulting in the decreased expressions of its protein, and of the c-Myc and Spl proteins (transcription factors of hTERT). These results indicate that the anticancer activity of Compound K could be mediated by inhibition of the telomerase activity.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.35-47
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• 2006

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) are well known as the most toxic environmental compound in these days. Many researches are reported that dioxin produces multiple toxic effects, such as endocrine toxicity, reproductive toxicity, immunotoxicity and cancer. In this study, we carried to discover novel evidence for previously unknown gene expression patterns in human exposed to dioxin by using radioactive cDNA microarray. 548 workers who were divided into experimental and control groups according to their urinary Naphthol levels were enrolled in our study. Blood mRNA in human was isolated, and the gene expression profiles were analyzed by cDNA microarray. Gene expression analysis identified 52 genes which exhibited a significant change. In our study, most notably, genes involved in cell cycle, cell proliferation, signal transduction and apoptosis in human exposed to dioxin, such as CCND3, TSHR, and EFRN5, were up-regulated. In the current study, we observed gene expression of people that are exposed to dioxin using radioactive cDNA microarray. Through these results, we suggest when objects are exposed to toxic compounds, such as dioxin, the radioactive cDNA microarray may be using in sensitively detecting of cancerous change.

• Journal of Life Science
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• v.17 no.12
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• pp.1634-1640
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• 2007

The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), nitric oxide (NO) scavenging activities and ferric- reducing/antioxidant power (FRAP) assay against extracts of Kalopanax pictus (KP) were measured. Radical scavenging and antioxidant activities were increased depend on the concentration and the effects were enhanced by ascorbic acid (AA). KP extracts and AA had a good anti-proliferating activity against HepG2 cells by MTT assay and induces cells apoptosis, which was demonstrated by flow cytometric analysis. KP extracts and AA caused the arrest of cell-cycle progression at either G0-G1-phase or G2/M-phase, which might be depending upon the KP extracts concentration. In addition, KP extracts and AA are effective in enhancing immunity and nitric oxide production by RAW 264.7 macrophages cells. KP extracts and AA inhibited tumor cell growth and exerted antioxidant effects as compared to controls. These results demonstrate that simultaneous AA and KP extracts treatment could be useful in preventing the oxidative damage and anti-proliferating HepG2 cells, and are effective in enhancing immunomodulatory and antioxidant activity.

• Journal of the Korean Wood Science and Technology
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• v.49 no.4
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• pp.371-383
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• 2021

Plant essential oils are used in products such as fragrances and cosmetics due to their individual aromatic characteristics. Currently, essential oils are not only used in cosmetics but also in pharmaceutical products with anti-bacterial, anti-viral, anti-fungal, anti-parasitic, insecticidal, anti-cancer, neuroprotective, psychophysiological, or anti-aging effects. Despite their pharmaceutical properties, some studies reported cytotoxic effects in high doses. Therefore, for pharmaceutical purposes, the margin of safety of essential oils needs to be examined. Herein, we evaluated the IC₅₀ of 10 essential oil from Korean native plants: Juniperus chinensis L. var. sargentii Henry, Citrus natsudaidai Hayata, Citrus reticulata Blanco, Citrus unshiu (Yu. Tanaka ex Swingle) Marcow, Artemisia capillaris Thunb, Aster glehnii F. Schmidt, Juniperus chinensis L, Zanthoxylum schinifolium Siebold & Zucc, Zanthoxylum piperitum (L.) D, and Cinnamomum loureirii. In addition, gene regulation of the cell-cycle gene and apoptosis marker CASP3 was examined at the IC₅₀ level. The purpose of this study was to describe the toxic concentrations of essential oils extracted from Korean native plants, thereby providing toxic concentration guidelines for inclusion in a toxicity database and in the application of plant essential oils in various fields.

• Journal of Animal Science and Technology
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• v.64 no.4
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• pp.752-769
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• 2022

Wheat gluten is an increasingly common ingredient in poultry diets but its impact on the small intestine in chicken is not fully understood. This study aimed to identify effects of high-gluten diets on chicken small intestines and the variation of their associated transcriptional responses by age. A total of 120 broilers (Ross Strain) were used to perform two animal experiments consisting of two gluten inclusion levels (0% or 25%) by bird's age (1 week or 4 weeks). Transcriptomics and histochemical techniques were employed to study the effect of gluten on their duodenal mucosa using randomly selected 12 broilers (3 chicks per group). A reduction in feed intake and body weight gain was found in the broilers fed a high-gluten containing diet at both ages. Histochemical photomicrographs showed a reduced villus height to crypt depth ratio in the duodenum of gluten-fed broilers at 1 week. We found mainly a significant effect on the gene expression of duodenal mucosa in gluten-fed broilers at 1 week (289 differentially expressed genes [DEGs]). Pathway analyses revealed that the significant DEGs were mainly involved in ribosome, oxidative phosphorylation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. These pathways are involved in ribosome protein biogenesis, oxidative phosphorylation and fatty acid metabolism, respectively. Our results suggest a pattern of differential gene expression in these pathways that can be linked to chronic inflammation, suppression of cell proliferation, cell cycle arrest and apoptosis. And via such a mode of action, high-gluten inclusion levels in poultry diets could lead to the observed retardation of villi development in the duodenal mucosa of young broiler chicken.

• Microbiology and Biotechnology Letters
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• v.32 no.1
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• pp.67-71
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• 2004

Pata de Vaca (Bauhinia forficata) Is a tree which grows naturally in the rainforests and tropical parts of Peru and Brazil, as well as tropical zones of Asia, eastern Paraguay and northeastern Argentina. The active fraction (Pata-50) of the 70% ethanol extract from Pata de Vaca was sequentially fractionated by HP-20 Diaion column chromatography and C-18 column chromatography, and its characteristics were investigated. The growth of all cancer cells tested except for MCF-7 was Inhibited in a concentration-dependent manner by Pata-50. Its $IC_{50}$ values were estimated to be 40.4 $\mu\textrm{g}$/$m\ell$ on AGS, 51.3 $\mu\textrm{g}$/$m\ell$ on HT-29, 52.1$\mu\textrm{g}$/$m\ell$ on HepG2, 65.2$\mu\textrm{g}$/$m\ell$ on A549, and 77.5$\mu\textrm{g}$/$m\ell$ on HeLa cells. A flow cytometric analysis of HepG2 cells revealed induction of apoptosis, but cell cycle regulation was not affected. The HepG2 cell population of apoptosis region increased In a concentration-dependent manner by Pata-50.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1637-1642
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• 2015

Background: RhoGTPase-activating proteins (RhoGAPs) regulate RhoGTPases in cells, but whether individual reactive oxygen species (ROS) regulate RhoGAPs is unknown. Our previous published papers have shown that deleted in liver cancer 1 (DLC1) inhibits cancer cell migration by its RhoGAP activity. The present study was designed to explore the role of $H_2O_2$ in regulation of DLC1. Materials and Methods: We treated cells with $H_2O_2$ for 24h and phenotypic changes were analyzed by MTT, RT-PCR, Western blotting, immunofluorescence staining and wound healing assays. Results: $H_2O_2$ downregulated cyclin D1 and cyclin E to inhibit proliferation, and upregulated BAX to induce apoptosis in MCF-7 cells. Compared with non-tumorigenic cells, $H_2O_2$ increased expression of DLC1 and reduced activity of RhoA in cancer cells. Stress fiber production and migration were also suppressed by $H_2O_2$ in MDA-MB-231 cells. Conclusions: Our study suggests that $H_2O_2$ inhibits proliferation through modulation of cell cycle and apoptosis-related genes, and inhibits migration by decreasing stress fibers via DLC1/RhoA signaling.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.859-865
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• 2006

With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).